Artificial bone and joint compositions and methods of use and manufacture

ABSTRACT

The present invention provides a ceramic porous body for in-vitro and in-vivo use comprising a composition comprising a calcium aluminate (CA) containing phase and optionally at least one of an accelerator, a retarder, a surfactant, a foaming agent, a reactive alumina, water, a fiber, and a biologically active material, and combinations thereof. Ceramic compositions are provides as well as method of using the ceramic compositions and methods of manufacturing a ceramic porous body. The ceramic porous bodies of this invention may be used as artificial bones, joints, in-vitro support structures, and in-vivo support structures for cells, tissues, organs, and nerve growth and regeneration.

BENEFIT OF PRIOR PATENT APPLICATIONS

This utility patent application is a divisional application of andclaims the benefit of prior U.S. Utility patent application Ser. No.10/924,502, filed Aug. 24, 2004, now U.S. Pat. No. 7,772,146, grantedAug. 10, 2010, which claims the benefit of U.S. Provisional PatentApplication Ser. No. 60/497,999 (now abandoned), filed Aug. 25, 2003,entitled “Artificial Bone And Joint Compositions And Methods Of Use AndManufacture” having the same named applicant as inventor, namely,Kenneth A. McGowan. The entire contents of U.S. Provisional PatentApplication Ser. No. 60/497,999 and U.S. Utility patent application Ser.No. 10/924,502 are incorporated by reference into this divisionalutility patent application.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The use of calcium aluminate (all associated phases, derivatives, and/oranalogs thereof) as a raw material for the manufacture of artificialbone, artificial joints, in-vitro support structures, and supportstructure for tissue, cells, and/or organ growth and/or regeneration isprovided. The use of slipcasting, slurrycasting or vibration casting inmolds to generate the desired shapes of the artificial bones, joints andsupport structures of the invention is also provided.

2. Description of the Background Art

Current artificial joints and bones are manufactured from apatites ormetal, typically titanium. They are machined to the desired shape whichis a costly and production inefficient method of construction. Thesematerials, in order to be accommodated by the host, must exhibitporosity so as to accommodate cell growth within the three dimensionalstructure. In particular, porosity is important where the part comes incontact with the host's natural structure (bone). This is due to theneed for the host's bone to grow into and vascularize the artificialstructure in order to develop the necessary bond between the two andreduce bone degeneration at the interface. Although attempts have beenmade in the current materials known by those skilled in the art tointroduce porosity, the resulting structure is less than ideal. In mostcases, artificial joints and other structures need to be replaced overtime because the surrounding tissue and structure has degenerated. Pins,screws, rods and other structures are required to stabilize, bond andsupport the interface.

There is an identifiable need to create structures designed to supporttissue growth, such as in artificial organ growth. The use of plasticsas a support structure for tissue growth is known by those skilled inthe art and has been accomplished by the use of organic polymers. Theseplastics and polymers are expensive when employed as artificialprostheses and lack porosity.

In spite of this background art, there remains a very real andsubstantial need for ceramic porous bodies comprising calcium aluminate,its phases, derivatives and/or analogs thereof, wherein the ceramicbodies are capable of functioning as artificial bone, artificial joints,in-vitro support structures, and in-vivo support structures for cells,tissues, organs and nerve growth and regeneration.

SUMMARY OF THE INVENTION

The present invention has met the above-described need. The porousceramic compositions of this invention provide compositions that may beused in the manufacture of artificial porous ceramic bodies that mayfunction as artificial bones and joints of a patient, as well asin-vitro support structures, in-vivo support structures for cells,tissues, organ and nerve growth and/or regeneration.

The present invention provides compositions comprising a calciumaluminate (CA) containing phase. Optionally, the compositions compriseat least one of a fiber, an accelerator, a retarder, a surfactant, afoaming agent, water, a biologically active material, one or morereactive aluminas, a source of phosphate, and combinations thereof. In apreferred embodiment, the compositions provide wherein the calciumaluminate containing phase results from the interaction of C_(n)A_(y),C_(n)A_(y)-hydrates, CaO, Al_(n)O_(y)-hydrates with P_(n)O_(y) ^(x) toform CAX, wherein n is an integer from about 1 to about 12, y is aninteger from about 1 to about 24, and x is an integer from about 1 toabout 12.

The present invention also provides for a method of making an artificialporous ceramic body comprising mapping a patient's identified bonestructure, creating a three dimensional pattern of said identified bonestructure from said mapped bone structure, creating a mold or negativeof said identified bone structure from said pattern, casting said moldemploying a composition comprising a calcium aluminate containing phase(CA) to form said artificial porous body. The compositions may be any ofthe compositions of this invention as described herein.

The present invention provides a porous ceramic body for in vitro and invivo use comprising the compositions of this invention as describedherein. The porous ceramic body of this invention has a porositysuitable for achieving vascularity.

Further, this invention provides for a method of using the ceramicporous composition of the present invention as described herein forproducing artificial structures for use in-vitro or in-vivo by a patientcomprising employing a porous ceramic composition of this invention,placing the porous ceramic composition into a mold wherein said moldmatches a patient's identified structure to form an artificialstructure.

The compositions, porous ceramic bodies and methods of this inventionwill be more fully understood from the following descriptions of theinvention and the claims appended hereto.

DETAILED DESCRIPTION OF THE INVENTION

Calcium aluminate (hereinafter “CA”) and its representative phases,analogs, and derivatives (including such as for example the introductionof phosphate containing phases resulting from the interaction ofC_(n)A_(y), C_(n) A_(y)-Hydrates, CaO, Al_(n)O_(y), andAl_(n)O_(y)-hydrates with P_(n)O_(y) ^(x)-referred herein as “CAX”) arebetter alternatives as an artificial material, wherein preferably, n isan integer from about 1 to 12 and y is an integer from about 1 to 24,and x is an integer from about 1 to 12. There are several reasons forthis including the fact that CAX contains hydratable compounds thatintroduce needed strength into the matrix. Porosity is easily introducedinto the structure via the aggregate itself and/or through the use of afoaming agent. The resulting ceramic matrix can be cast to a specificshape with ease using casting technology known by those persons skilledin the art, such as including, slip casting, slurry casting or vibrationcasting into molds to generate a desired shape. The resulting materialis chemically compatible with bone and other biological processes. Theresulting shape can be high fired to make it unreactive with itsenvironment, if desired, or, it can be partially fired to leave itsomewhat active. Furthermore, a hollow cavity within the structure canbe created to better allow vascularity to occur and to allow marrow toexist if indeed the body will begin to produce it with the presence ofvascularity. Both conditions of vascularity and marrow growth willfoster the progress of each process.

The present invention provides an artificial prosthesis having the CAXmaterial as a structure to support tissue growth. It can bepre-engineered to match the desired finished structure and in addition,in the form of hydrates, these materials will slowly be metabolized bythe body. Because of the nature of the compounds, they can easily bederivatized and functionalized for use with biological processes, suchas for example, but not limited to, accommodating protein buildingblocks, and binding sites.

The present invention provides artificial prosthesis structures and amethod for the manufacture of an artificial prosthesis. The methodincludes mapping the structure of interest by digitizing data from MRIscans (if soft tissue), X-ray data (if bone structure) or a combinationof both, digitizing the data to create a three dimensional pattern orblank of the structure as known by those skilled in the art, utilizingthe blank or pattern to create a mold or negative of the structure ofinterest, casting within the mold CA, CAX, and/or derivatives, and/oranalogs of CA or CAX, of this invention, and optionally addingbiologically active materials to produce an artificial prosthesis. Theresulting artificial prosthesis is then further processed, if desired.This may involve a firing process to fix certain desired mineralogicalphases and/or chemically activated by an immersion process known bythose persons skilled in the art.

The present invention provides a porous ceramic body for in vitro and invivo use comprising a calcium aluminate (CA) containing phase. Inpreferred embodiments of this invention the porous ceramic body furthercomprises one of a foaming agent, a fiber, a source of phosphate, anaccelerator, a retarder, a surfactant, reactive alumina, a biologicallyactive material, and combinations thereof.

In another embodiment of this invention the porous ceramic body asdescribed includes wherein the calcium aluminate containing phasecomprises one or more phases, analogs and derivatives of calciumaluminate.

In a preferred embodiment of this invention, the porous ceramic body asdescribed herein includes wherein the calcium aluminate containing phaseresults from the interaction of C_(n)A_(y), C_(n)A_(y)-hydrates, CaO,Al_(n)O_(y)-hydrates with P_(n)O_(y) ^(x) to form CAX, wherein n is aninteger from about 1 to about 12, y is an integer from about 1 to about24, and x is an integer from about 1 to about 12.

In another embodiment of this invention, a porous ceramic composition isprovided that comprises a calcium aluminate (CA) containing phase, aretarder, and a surfactant, wherein said calcium aluminate containingphase results from the interaction of C_(n)A_(y), C_(n)A_(y)-hydrates,CaO, Al_(n)O_(y)-hydrates with P_(n)O_(y) ^(x) to form CAX, wherein n isan integer from about 1 to about 12, y is an integer from about 1 toabout 24, and x is an integer from about 1 to about 12. The porousceramic composition optionally further comprises at least one of afiber, water, an accelerator, a biologically active material, a sourceof phosphate, a reactive alumina, and combinations thereof.

In yet another embodiment of this invention, a method is provided forusing a ceramic porous composition for producing artificial structuresfor use in-vitro or in-vivo by a patient comprising employing a porousceramic composition comprising a calcium aluminate (CA) containingphase, a retarder, and a surfactant, as described herein, placing saidporous ceramic composition into a mold wherein said mold matches apatient's pre-identified structure to form an artificial structure. Themethod includes wherein said calcium aluminate containing phase resultsfrom the interaction of C_(n)A_(y), C_(n)A_(y)-hydrates, CaO,Al_(n)O_(y)-hydrates with P_(n)O_(y) ^(x) to form CAX, wherein n is aninteger from about 1 to about 12, y is an integer from about 1 to about24, and x is an integer from about 1 to about 12. The present ceramicporous composition may also be used as an in-situ patch for repairing abone void of the patient that may occur, for example but not limited to,as a result of trauma and injury to the bone.

The following examples demonstrate the instant invention in greaterdetail. These examples are not intended to limit the scope of theinvention in any way.

Example 1

Wt. % Calcium Aluminate (various phases) 99 Citric Acid Monohydrate 0.2Castament FS20 0.55 Herculon 153 fibers 0.25 Water (for casting as a‘plus’ addition) 22.0

In this example an inert mold of the object would be created from thethree dimensional data. Common mold materials are aluminum, steel, PVCor polyurethane. Water would be added to the above mix to give it avibration cast consistency. This mix would then be vibrated into themold. In other examples the water addition, additives and consistency ofthe material could be adjusted to allow for slip casting or gel casting.The water demand of the mixture is controlled by the particle sizedistribution of the mix and also the surfactant (in Example 1, CastamentFS20). Examples of other surfactants are, but not limited to, sodiumtripolyphosphate (STP or STPP), Darvan #7, and Melflux. As will beunderstood by those person skilled in the art, the choice of surfactantshall affect the water demand and associated additive concentrationssuch that they will need to be adjusted, accordingly. In examples 1-4,water added was kept constant in order to compare other resultingproperties. A typical water range can be from about 5%-75%.

The material would be allowed to ‘set’ (precipitation of the CA-hydratephases). The speed of this reaction is slowed by the addition of citricacid monohydrate. Other materials that can control the reaction or ‘set’time are, for example but not limited to, boric acid and anhydrouscitric acid (as retarders) and lithium carbonate, sodium silicate orsodium aluminate (as accelerators).

The ‘set’ results in a shape exhibiting strong mechanical properties ina mechanism very similar to that of concrete. The mold would then bestripped and the shape and dried in an oven at approximately 110 degreesCelsius (C). In this form the shape would be composed of various CalciumAluminate phases and Calcium Aluminate hydrate phases, alumina gel,alumina (present in the CA starting material), Herculon 153 fibers(given as an example but substitution of biocompatible fiber can beaccomplished). Typically this shape would now be fired at about 1000° C.During the firing process the CA-hydrates and alumina gel will beconverted to the unhydrated phases (primarily CA and CA₂) and thealumina gel will convert to the oxide. This process will also introduceporosity in place of the chemically combined water and the organicfiber. The organic fiber is introduced to allow for interconnectedporosity after burn-out. The diameter of the resulting channels isdetermined by controlling the diameter of the starting fiber. Thepresence of the fiber also gives water a pathway of escape from theshape, although this is not critical in small shapes. The resultingshape is suitable as scaffoldings or as an artificial bone structurecapable of supporting stem cells that will differentiate intoosteoblasts (in the case of bone). In addition, this structure can nowbe chemically altered to accommodate binding of proteins or otherbioactive factors, promoting bone growth, for example. Once introducedin vivo, the matrix will again begin to hydrate which will allowbio-decomposition to occur while natural bone is being formed. If duringthe firing process, the shape is exposed to temperatures near 1550° C.,CA₆ will be formed and re-hydration will not occur. In some cases thismay be desirable, for example hip replacement, where a well definedgeometric structure needs to be maintained.

A variety of other compositional examples are given here with a shortexplanation of possible benefits.

Example 2

Wt. % Calcium Aluminate (various phases) 84 Citric acid monohydrate 0.2Reactive aluminas 15 STPP 0.55 Herculon 153 fibers 0.25 Water (forcasting as a ‘plus’ addition) 22.0In this example reactive aluminas such as ALMATIS' A-2, A-3000 andA-1000 are added to give improved casting character and a denser, lessporous final matrix. Herculon 153 fibers are fibrous materialscommercially available from Hercules, Incorporated, Wilmington, Del.Darvan #7 is a sodium polymethacrylate composition used as a surfactantand is commercially available from R. T. Vanderbilt Company, Inc.,Norwalk, Conn.

Example 3

Wt. % Calcium Aluminate (various phases) 98.5 Foaming agent 1.0 Darvan#7 0.5 Water (for casting as a ‘plus’ addition) 22.0In this example a foaming agent such as CF-500 or CF-700 from Unifoam,is used to introduce a high degree of porosity to the finished material.The diameter of the porosity can be controlled by the choice of foamingagent (e.g. CF-700 gives a larger bubble) and the volume of porosity iscontrolled by the amount of foaming agent added.

Example 4

Wt. % Calcium Aluminate (various phases) 90.5 Foaming agent 1.0 Calciumorthophosphate 8.0 Melflux 0.5 Water (for casting as a ‘plus’ addition)22.0In this example a phosphate source is added to give raw material forosteoblast precipitation of natural bone. Melflux is a polymericsurfactant commercially available from Degussa Construction Polymers,Kennesaw, Ga.

As can be seen in these examples there are a variety of strategies onecan take in determining an appropriate starting matrix. The examples setforth herein are given to demonstrate this breadth, however, they arenot intended to limit the scope of the present invention as describedherein. These examples set forth herein are for the purposes ofillustration and it will be evident to those persons skilled in the artthat numerous variations and details of the instant invention may bemade without departing from the instant invention as set forth herein.

Example 5 Detailed Compositional Strategy

Example 5 will be used to demonstrate a detailed compositional matrixand the resulting physical properties of the resulting solid body.

Calcium Aluminate Clinker of the following chemistry (reported on anoxide basis) was obtained for the study. The material was screened,sized and chemistry was determined on each fraction (see table I)

Fraction +10 m 10/28 m 28/65 m −65 m Oxide (concentration in Wt %) SiO₂0.44 0.29 0.22 0.25 Al₂O₃ 71.59 71.21 70.35 71.19 Fe₂O₃ 0.07 0.01 <0.010.01 CaO 27.38 28.08 29.02 27.95 MgO 0.27 0.22 0.21 0.31 Na₂O 0.23 0.170.18 0.26 K₂O 0.01 0.01 0.01 0.02 P₂O₅ 0.01 0.01 0.01 0.01

Mineralogical Examination of these fractions showed the following:

+10 m 10/28 m 28/65 m −65 Compound Present CaAl₂O₄ (CA) M M M M CaAl₄O₇(CA₂) M M M M Ca₁₂Al₁₄O₃₃ (C₁₂A₇) m m t nd Ca₃Al₂O₆ (C₃A) nd nd nd ndCa₅Al₆O₁₄ (C₅A₃) nd nd nd nd Ca₂Al₁₂O₅ (C₂A) nd nd nd nd CaAl₁₂O₁₉ (CA₆)nd nd nd nd Ca₃Al₁₀O₁₈ (C₃A₅) nd nd nd nd CaO (C) t t t t Al₂O₃ (A) t tt t M = Major, m = minor, t = trace, nd = not detected

This chemistry and mineralogy is typical for a 70% alumina containing CAcement. CA cements containing greater than 70% alumina can be used. CAcement containing less than 70% alumina can also be used; however, mostcommercially available products have impurities, which increase inconcentration as the alumina content decreases. Common brands of 70%alumina containing CA cement are ALAMITIS' CA14 product and Lafarge'sSecar 71 product.

The typical average open porosity of the CA aggregate is 53.5% while theTSG averages 2.9 g/cm³.

Composition Example 5

Aggregate Wt % CA +10 m 15% CA 10/28 m 30% CA 28/65 m 10% CA −65 m 11%CA −325 m  7% A-2 alumina  8% A-3000 alumina 10% A-1000 alumina  9% STPP(plus addition) 0.15%  

24% by weight of water was added to give a vibration cast consistency.The material was cast into simple bars in order to determine modulus andcrushing strengths. The shape was stripped from the mold in 24 hours anddried at 110° C. Finally, the shape was fired to a temperature of 1100°C. and allowed to reach thermal equilibrium. The shape was allowed tocool and was tested. The results are as follows:

Apparent porosity=50%

Average pore size=44 microns

Cold crushing strength (ASTM C133)=34.5 MPa

Modulus of Rupture (ASTM C133)=9.3 MPa

Whereas particular embodiments of this invention have been describedabove for purposes of illustration, it will be evident to those personsskilled in the art that numerous variations of the details of thepresent invention may be made without departing from the invention asdefined herein and in the appended claims.

What is claimed is:
 1. A porous ceramic composition consistingessentially of: a calcium aluminate (CA) containing phase having theformula C_(n)A_(y), wherein n is an integer from about 1 to about 12 andy is an integer from about 1 to about 24, said CA containing phasehaving at least a CaAl₂O₄ phase and a CaAl₄O₇ phase, including phosphatecontaining phases resulting from the interaction of C_(n)A_(y),C_(n)A_(y)-hydrates wherein n is an integer from about 1 to about 12 andy is an integer from about 1 to about 24, CaO, Al_(n)O_(y), andAl_(n)O_(y)-hydrates wherein n is an integer from about 1 to about 12and y is an integer from about 1 to about 24 with P_(n)O_(y) ^(x),wherein in the formula P_(n)O_(y) n is an integer 1, 2, or 3 and y is aninteger 3, 4, or 7 and x is a negatively charged integer of 1, 3, or 4;and a biologically active material that comprises one or more proteinsfor promoting bone growth.
 2. The porous ceramic composition of claim 1further including interconnected porosity.
 3. The porous ceramiccomposition of claim 1 that supports stem cells.
 4. The porous ceramiccomposition of claim 3 wherein said stem cells differentiate intoosteoblasts.
 5. The ceramic porous composition of claim 1 that isrehydrated in-vivo.
 6. The porous ceramic composition of claim 1 furtherincluding wherein said phosphate is a raw material for osteoblastprecipitation of natural bone.
 7. The porous ceramic composition ofclaim 6 wherein said phosphate is calcium orthophosphate.